A single topical application of the thrombin-derived peptide TRAP- 508 accelerates wound healing through enhancement of neutrophil recruitment, collagen deposition, granulation tissue formation, vascularization, and wound epithelization. We, therefore, propose to develop products to overcome chronic wound defects. Many proposed therapies appear not to be cost-effective because of high product cost and marginal effectiveness in clinical trials. Based on preliminary data, it appears that TRAP-508 products may be much more effective than other growth factor-based technologies in stimulating healing of chronic wounds and much less expensive. We, therefore, propose a "Fast-Track" approach to proceed through Phase II, regulatory requirements, and to begin clinical trials as quickly as possible. Our objective in Phase I is to determine TRAP- 508 effectiveness in specific chronic wound models and define selective advantages in its mode of action on which to base proceeding into Phase II product development. In these studies, we will: 1) determine the efficacy of TRAP-508 in two ischemic wound healing models; 2) determine the half-life of TRAP-508 in chronic wound fluid; and 3) determine if TRAP-508 inhibits or limits production of collagenase and other metalloproteases that appear to contribute to prolonged inflammatory and tissue destructive phases of repair associated with chronic wounds. Chronic wounds, including diabetic ulcers, venous stasis ulcers, pressure sores, severe bums and other non-healing wounds, are a critical problem in today's healthcare system. These wounds are associated with extremely high treatment costs and are of great risk to patients. Chronic, non-healing diabetic and vascular ulcers are suffered by 2.6 million people (with 120,000 amputations each year), serious bums affect 2. 1 million people, and there are 1 million bone grafts and repairs of joints, ligaments, or tendons. TRAP-508 has the potential to greatly improve the quality of care for these people within a short period of time.